Certain 5H-dibenzo[a,d]cycloheptene compounds having aminoalkyl substituents at the 5-position have been prepared in the past using a 5H-dibenzo[a,d]cycloheptene-5-one compound as starting material using a variety of circuitous routes to introduce the 5-position aminoalkyl side chain without affecting double bonds or other functional substituents susceptible to attack by catalytic hydrogenation. Included are the 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes having other susceptible substituents in the molecule.
A preferred group of such compounds have the following structural formula: ##STR1## wherein Y is a loweralkoxy substituent or an amino substituent which may be mono- or dialkylated, e.g., ##STR2##
X and X.sup.1 are similar or dissimilar and are selected from hydrogen, an alkyl group having up to 6 carbon atoms, an alkenyl group having up to 6 carbon atoms, a perfluoroalkyl group having up to 4 carbon atoms, a phenyl or a substituted phenyl radical, an amino, an alkylamino group having up to 4 carbon atoms, a dialkylamino group having up to 8 carbon atoms, an alkylsulfonylamino group having up to 4 carbon atoms, halogen (fluorine, chlorine, bromine, or iodine), hydroxyl, an alkoxyl group having up to 4 carbon atoms, a perfluoroalkoxyl group having up to 4 carbon atoms, an alkylmercapto group having up to 4 carbon atoms, a perfluoroalkylmercapto group having up to 4 carbon atoms, an alkylsulfonyl group having up to 4 carbon atoms, a perfluoroalkylsulfonyl group having up to 4 carbon atoms, sulfamoyl, an alkylsulfamoyl group having up to 4 carbon atoms, or a dialkylsulfamoyl group having up to 8 carbon atoms; more than one of these substituents may be on each benzenoid ring and the compounds may have substituents on the propyl chain such as lower alkyl radicals, preferably having from 1 to 4 carbon atoms;
R.sub.1 and R.sub.2 are each either hydrogen, an alkyl of 1-5 carbons (including branched chain alkyl), or cycloalkyl substituents containing 1-5 carbons, for example, N-methyl-5H-dibenzo[a,d]cycloheptene-5-propylamine; and
R.sub.3 is alkyl of 1-5 carbons.
Certain of these prior art methods are described in U.S. Pat. No. 3,372,196 of Edward L. Engelhardt and in a publication of Engelhardt et al., J. Med. Chem., 11, 326-332 (1968). One such typical method begins with 5H-dibenzo[a,d]cycloheptene-5-one and first converts the ketone to the corresponding 5-hydroxy compound by reduction with borohydride followed by treatment with dry hydrogen chloride to produce the corresponding 5-chloro-5H-dibenzo[a,d]cycloheptene. This compound is then coupled with a Grignard reagent derived from dimethylaminopropyl chloride to produce the desired N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-5-propylamine which is demethylated to the corresponding N-methyl derivative. Another method, disclosed in the above-mentioned patent, to prepare compounds of the type described involves the reaction of a 5H-dibenzo[a,d]cycloheptene-5-one with an alkoxypropyl magnesium halide to produce the corresponding 5-alkoxypropyl-5-hydroxy-5H-dibenzo[a,d]cycloheptene and reducing this compound using hydrogen iodide in acetic anhydride to produce a 5-(3-iodopropyl)-5H-dibenzo[a,d]cycloheptene in low yield. This compound is then reacted with ammonia or a lower alkyl or dialkyl amine to produce the corresponding 5-(3-aminopropyl, 3-alkylaminopropyl, or 3-dialkylaminopropyl)-5H-dibenzo[a,d]cycloheptene. Compounds of this type have tetrabenazine antagonist activity and are useful in the treatment of humans affected by depression as reported in the above-noted J. Med. Chem. article or as disclosed in the above-noted U.S. Pat. No. 3,372,196 of Engelhardt or are useful as intermediates in the preparation of such compounds.